Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model

Tumour self-seeding by circulating tumour cells (CTCs) enhances tumour progression and recurrence. Previously, we demonstrated that tumour self-seeding by CTCs occurs in osteosarcoma and revealed that interleukin-6 (IL-6) may promote CTC attraction. Here, we investigated the underlying mechanisms of...

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Published in:Oncotarget 2016-01, Vol.7 (1), p.446-458
Main Authors: Zhang, Yinglong, Ma, Qiong, Liu, Tao, Guan, Guofeng, Zhang, Kailiang, Chen, Jiayan, Jia, Nan, Yan, Shiju, Chen, Guanyin, Liu, Shiluan, Jiang, Kuo, Lu, Yao, Wen, Yanhua, Zhao, Haien, Zhou, Yong, Fan, Qingyu, Qiu, Xiuchun
Format: Article
Language:English
Subjects:
Animals
Blotting, Western
Bone Neoplasms - blood
Bone Neoplasms - genetics
Bone Neoplasms - metabolism
Cell Line
Cell Line, Tumor
Female
Humans
Interleukin-6 - genetics
Interleukin-6 - metabolism
Janus Kinases - metabolism
Mice, Nude
Microscopy, Fluorescence
Mitogen-Activated Protein Kinases - metabolism
Neoplasm Seeding
Neoplastic Cells, Circulating - metabolism
Osteosarcoma - blood
Osteosarcoma - genetics
Osteosarcoma - metabolism
Research Paper
Reverse Transcriptase Polymerase Chain Reaction
RNA Interference
Signal Transduction - genetics
STAT3 Transcription Factor - metabolism
Transplantation, Heterologous
Online Access:Get full text
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Summary:Tumour self-seeding by circulating tumour cells (CTCs) enhances tumour progression and recurrence. Previously, we demonstrated that tumour self-seeding by CTCs occurs in osteosarcoma and revealed that interleukin-6 (IL-6) may promote CTC attraction. Here, we investigated the underlying mechanisms of IL-6 in tumour self-seeding by CTCs. IL-6 suppression inhibited in vitro cell proliferation, migration, and invasion. In addition, rhIL-6 activated the Janus-activated kinase/signal transducers and activators of transcription 3 (JAK/STAT3) and mitogen-activated protein kinase/extracellular-signal regulated kinase1/2 (MAPK/ERK1/2) pathways in vitro. Both pathways increased cell proliferation, but only the JAK/STAT3 pathway promoted migration. Suppressing IL-6 inhibited in vivo tumour growth and metastasis. IL-6 suppression or JAK/STAT3 pathway inhibition reduced CTC seeding in primary tumours. Collectively, IL-6 promotes tumour self-seeding by CTCs in a nude mouse model. This finding may provide a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence.
ISSN:1949-2553
DOI:10.18632/oncotarget.6371